Choriocapillaris microvasculature dysfunction in systemic hypertension

Jacqueline Chua, Thu-Thao Le, Bingyao Tan, Mengyuan Ke, Chi Li, Damon Wing Kee Wong, Anna C S Tan, Ecosse Lamoureux, Tien Yin Wong, Calvin Woon Loong Chin, Leopold Schmetterer, Jacqueline Chua, Thu-Thao Le, Bingyao Tan, Mengyuan Ke, Chi Li, Damon Wing Kee Wong, Anna C S Tan, Ecosse Lamoureux, Tien Yin Wong, Calvin Woon Loong Chin, Leopold Schmetterer

Abstract

We examined the choriocapillaris microvasculature using a non-invasive swept-source optical coherence tomography angiography (SS-OCTA) in 41 healthy controls and 71 hypertensive patients and determined possible correlations with BP and renal parameters. BP levels, serum creatinine and urine microalbumin/creatinine ratio (MCR) specimens were collected. The estimated glomerular filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation. The main outcome was choriocapillaris flow deficits (CFD) metrics (density, size and numbers). The CFD occupied a larger area and were fewer in number in the hypertensive patients with poor BP control (407 ± 10 µm2; 3260 ± 61) compared to the hypertensives with good BP control (369 ± 5 µm2; 3551 ± 41) and healthy controls (365 ± 11 µm2; 3581 ± 84). Higher systolic BP (β = 9.90, 95% CI, 2.86-16.93), lower eGFR (β = - 0.85; 95% CI, - 1.58 to - 0.13) and higher urine MCR (β = 1.53, 95% CI, 0.32-2.78) were associated with larger areas of CFD. Similar significant associations with systolic BP, eGFR and urine MCR were found with number of CFD. These findings highlight the potential role of choriocapillaris imaging using SS-OCTA as an indicator of systemic microvascular abnormalities secondary to hypertensive disease.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Distribution of (A) density, (B) size and (C) number of choriocapillaris flow deficits (CFD) in participants without hypertension (healthy controls), hypertensives with good blood pressure control and hypertensives with poor blood pressure control. Data and P values shown are after adjustment for age, gender, race and body mass index. Hypertensives with poor blood pressure control had the largest and fewest CFD than hypertensives with good blood pressure control and healthy controls.
Figure 2
Figure 2
Swept source optical coherence tomography angiography (SS-OCTA; 3 × 3 mm2 area) and color‐coded maps indicating regions of choriocapillaris flow deficits (CFD) (B, D and F) of a choriocapillaris vascular layer of a healthy control individual (Top panel; AB), a hypertensive with well-controlled blood pressure (Middle panel; CD), and a hypertensive with poorly controlled blood pressure (Bottom panel; EF). Hypertensives with high BP tended to have larger sized CFD (F; labelled as yellow). The presence of flow deficits is areas of dark regions in the angiogram (A, C and E) and their sizes are color‐coded (B, D and F). Images (A, C and E) were generated from the built-in review software (PLEX Elite Review Software, Carl Zeiss Meditec, Inc., Dublin, USA; Version 1.7.1.31492; https://www.zeiss.fr/content/dam/Meditec/international/ifu/documents/plex-elite/current/2660021169042_rev_a_artwork.pdf). The images (B, D and F) were generated from MATLAB software (The MathWorks, Inc.; Version R2018b; https://www.mathworks.com/products/new_products/release2018b.html).
Figure 3
Figure 3
Schematic log–log plot concerning flow deficits where the data follow a y = mx + b slope intercept relationship between the number of flow deficits and size of flow deficits. Flow deficits that are larger regions, as shown along the right side of the slope, are more likely to occur in persons with poorly controlled blood pressure (BP).
Figure 4
Figure 4
Scatterplots showing (A) positive correlation of size of flow deficits with systolic blood pressure and (B) negative correlation of number of flow deficits with systolic blood pressure in participants without hypertension (healthy controls; green), hypertensives with good blood pressure control (red) and hypertensives with poor blood pressure control (green).

References

    1. Lim SS, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–2260. doi: 10.1016/S0140-6736(12)61766-8.
    1. Struijker-Boudier HA, Heijnen BF, Liu YP, Staessen JA. Phenotyping the microcirculation. Hypertension. 2012;60:523–527. doi: 10.1161/HYPERTENSIONAHA.111.188482.
    1. Struijer-Boudier H. Microcirculation in hypertension. Eur. Heart J. Suppl. 1999;1:L32–L37.
    1. Cheung CY, Ikram MK, Sabanayagam C, Wong TY. Retinal microvasculature as a model to study the manifestations of hypertension. Hypertension. 2012;60:1094–1103. doi: 10.1161/HYPERTENSIONAHA.111.189142.
    1. Sabanayagam C, et al. Retinal microvascular caliber and chronic kidney disease in an Asian population. Am. J. Epidemiol. 2009;169:625–632. doi: 10.1093/aje/kwn367.
    1. Sabanayagam C, et al. Retinal arteriolar narrowing increases the likelihood of chronic kidney disease in hypertension. J. Hypertens. 2009;27:2209–2217. doi: 10.1097/HJH.0b013e328330141d.
    1. Kawasaki R, et al. Retinal vessel diameters and risk of hypertension: The multiethnic study of atherosclerosis. J. Hypertens. 2009;27:2386–2393. doi: 10.1097/HJH.0b013e3283310f7e.
    1. Ding J, et al. Retinal vascular caliber and the development of hypertension: A meta-analysis of individual participant data. J. Hypertens. 2014;32:207–215. doi: 10.1097/HJH.0b013e32836586f4.
    1. Smith W, et al. Retinal arteriolar narrowing is associated with 5-year incident severe hypertension: The Blue Mountains Eye Study. Hypertension. 2004;44:442–447. doi: 10.1161/.
    1. Wong TY, Shankar A, Klein R, Klein BE, Hubbard LD. Prospective cohort study of retinal vessel diameters and risk of hypertension. BMJ. 2004;329:79. doi: 10.1136/bmj.38124.682523.55.
    1. Kashani AH, et al. Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications. Prog. Retin. Eye Res. 2017;60:66–100. doi: 10.1016/j.preteyeres.2017.07.002.
    1. Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Progr. Retin. Eye Res. 2017 doi: 10.1016/j.preteyeres.2017.11.003.
    1. Sun C, et al. Systemic hypertension associated retinal microvascular changes can be detected with optical coherence tomography angiography. Sci. Rep. 2020;10:9580. doi: 10.1038/s41598-020-66736-w.
    1. Chua J, et al. Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography. J. Hypertens. 2018 doi: 10.1097/HJH.0000000000001916.
    1. Donati S, et al. Optical coherence tomography angiography and arterial hypertension: A role in identifying subclinical microvascular damage? Eur. J. Ophthalmol. 2019 doi: 10.1177/1120672119880390.
    1. Hua D, et al. Retinal microvascular changes in hypertensive patients with different levels of blood pressure control and without hypertensive retinopathy. Curr. Eye Res. 2020 doi: 10.1080/02713683.2020.1775260.
    1. Hua D, et al. Use of optical coherence tomography angiography for assessment of microvascular changes in the macula and optic nerve head in hypertensive patients without hypertensive retinopathy. Microvasc. Res. 2020;129:103969. doi: 10.1016/j.mvr.2019.103969.
    1. Lee WH, et al. Retinal microvascular change in hypertension as measured by optical coherence tomography angiography. Sci. Rep. 2019;9:156. doi: 10.1038/s41598-018-36474-1.
    1. Lim HB, et al. Changes in ganglion cell-inner plexiform layer thickness and retinal microvasculature in hypertension: An optical coherence tomography angiography study. Am. J. Ophthalmol. 2019;199:167–176. doi: 10.1016/j.ajo.2018.11.016.
    1. Pascual-Prieto J, et al. Utility of optical coherence tomography angiography in detecting vascular retinal damage caused by arterial hypertension. Eur. J. Ophthalmol. 2020;30:579–585. doi: 10.1177/1120672119831159.
    1. Shin YI, et al. Peripapillary microvascular changes in patients with systemic hypertension: An optical coherence tomography angiography study. Sci. Rep. 2020;10:6541. doi: 10.1038/s41598-020-63603-6.
    1. Ferrara D, Waheed NK, Duker JS. Investigating the choriocapillaris and choroidal vasculature with new optical coherence tomography technologies. Prog. Retin. Eye Res. 2016;52:130–155. doi: 10.1016/j.preteyeres.2015.10.002.
    1. Spaide RF. Choriocapillaris flow features follow a power law distribution: Implications for characterization and mechanisms of disease progression. Am. J. Ophthalmol. 2016;170:58–67. doi: 10.1016/j.ajo.2016.07.023.
    1. Chua J, et al. Impact of systemic vascular risk factors on the choriocapillaris using optical coherence tomography angiography in patients with systemic hypertension. Sci. Rep. 2019;9:5819. doi: 10.1038/s41598-019-41917-4.
    1. Takayama K, et al. Novel classification of early-stage systemic hypertensive changes in human retina based on OCTA measurement of choriocapillaris. Sci. Rep. 2018;8:15163. doi: 10.1038/s41598-018-33580-y.
    1. Lane M, et al. Visualizing the choriocapillaris under drusen: Comparing 1050-nm swept-source versus 840-nm spectral-domain optical coherence tomography angiography. Invest. Ophthalmol. Vis. Sci. 2016;57:585–590. doi: 10.1167/iovs.15-18915.
    1. Terheyden JH, et al. Retinal and choroidal capillary perfusion are reduced in hypertensive crisis irrespective of retinopathy. Transl. Vis. Sci. Technol. 2020;9:42. doi: 10.1167/tvst.9.8.42.
    1. Wong TY, Klein R, Klein BE, Meuer SM, Hubbard LD. Retinal vessel diameters and their associations with age and blood pressure. Invest. Ophthalmol. Vis. Sci. 2003;44:4644–4650. doi: 10.1167/iovs.03-0079.
    1. de Carlo TE, Romano A, Waheed NK, Duker JS. A review of optical coherence tomography angiography (OCTA) Int. J. Retin. Vitreous. 2015;1:5. doi: 10.1186/s40942-015-0005-8.
    1. Johnson MA, et al. Ocular structure and function in an aged monkey with spontaneous diabetes mellitus. Exp. Eye Res. 2005;80:37–42. doi: 10.1016/j.exer.2004.08.006.
    1. Zhang Q, et al. A novel strategy for quantifying choriocapillaris flow voids using swept-source OCT angiography. Invest. Ophthalmol. Vis. Sci. 2018;59:203–211. doi: 10.1167/iovs.17-22953.
    1. Farrah TE, Dhillon B, Keane PA, Webb DJ, Dhaun N. The eye, the kidney, and cardiovascular disease: Old concepts, better tools, and new horizons. Kidney Int. 2020;98:323–342. doi: 10.1016/j.kint.2020.01.039.
    1. Chua J, et al. Optical coherence tomography angiography in diabetes and diabetic retinopathy. J. Clin. Med. 2020 doi: 10.3390/jcm9061723.
    1. Akahori T, Iwase T, Yamamoto K, Ra E, Terasaki H. Changes in choroidal blood flow and morphology in response to increase in intraocular pressure. Invest. Ophthalmol. Vis. Sci. 2017;58:5076–5085. doi: 10.1167/iovs.17-21745.
    1. Zheng F, et al. Quantitative OCT angiography of the retinal microvasculature and choriocapillaris in highly myopic eyes with myopic macular degeneration. Br. J. Ophthalmol. 2021 doi: 10.1136/bjophthalmol-2020-317632.
    1. Goh VJ, et al. Novel Index of maladaptive myocardial remodeling in hypertension. Circul. Cardiovasc. Imaging. 2017 doi: 10.1161/CIRCIMAGING.117.006840.
    1. Gupta P, et al. Rationale and Methodology of The PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study [PIONEER] Aging Dis. 2020 doi: 10.14336/ad.2020.0206.
    1. Hong J, et al. Intra-session repeatability of quantitative metrics using widefield optical coherence tomography angiography (OCTA) in elderly subjects. Acta Ophthalmol. 2019 doi: 10.1111/aos.14327.
    1. Chua J, et al. Inter-relationship between ageing, body mass index, diabetes, systemic blood pressure and intraocular pressure in Asians: 6-year longitudinal study. Br. J. Ophthalmol. 2018 doi: 10.1136/bjophthalmol-2018-311897.
    1. Shen SY, et al. The prevalence and types of glaucoma in malay people: The Singapore Malay eye study. Invest. Ophthalmol. Vis. Sci. 2008;49:3846–3851. doi: 10.1167/iovs.08-1759.
    1. Wong TY, et al. Prevalence and risk factors for diabetic retinopathy: The Singapore Malay Eye Study. Ophthalmology. 2008;115:1869–1875. doi: 10.1016/j.ophtha.2008.05.014.
    1. Kawasaki R, et al. Prevalence of age-related macular degeneration in a Malay population: The Singapore Malay Eye Study. Ophthalmology. 2008;115:1735–1741. doi: 10.1016/j.ophtha.2008.02.012.
    1. Levey AS, et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009;150:604–612. doi: 10.7326/0003-4819-150-9-200905050-00006.
    1. Lin E, et al. Are choriocapillaris flow void features robust to diurnal variations? A swept-source optical coherence tomography angiography (OCTA) study. Sci. Rep. 2020;10:11249. doi: 10.1038/s41598-020-68204-x.

Source: PubMed

3
Abonneren